Agonistic Interleiukin 15 Complexes and Uses Thereof

Abstract

The present disclosure provides agonistic IL-15 complexes that have therapeutic use, and methods for making such proteins. The present disclosure additionally provides methods of treating disease in a subject in need thereof by administering such agonistic IL-15 complexes.

We claim: 
     
         1 . A fusion protein comprising an interleukin-15 (IL-15) receptor α sushi domain fused to an Fc monomer, wherein the IL-15 receptor α sushi domain comprises the amino acid sequence of SEQ ID NO: 5 and the Fc monomer comprises the amino acid sequence of SEQ ID NO: 6. 
     
     
         2 . The fusion protein of  claim 1 , wherein the carboxyl-terminus of the IL-15 receptor α sushi domain is fused to the amino-terminus of the Fc monomer via a linker having the amino acid sequence of SEQ ID NO: 7. 
     
     
         3 . A protein complex comprising the fusion protein of  claim 1  and an IL-15. 
     
     
         4 . The protein complex of  claim 3 , wherein the IL-15 comprises the amino acid sequence of SEQ ID NO: 3. 
     
     
         5 . The protein complex of  claim 3 , wherein the IL-15 comprises the amino acid sequence of SEQ ID NO: 4. 
     
     
         6 . A protein complex comprising the fusion protein of  claim 2  and an IL-15. 
     
     
         7 . The protein complex of  claim 6 , wherein the IL-15 comprises the amino acid sequence of SEQ ID NO: 3. 
     
     
         8 . The protein complex of  claim 6 , wherein the IL-15 comprises the amino acid sequence of SEQ ID NO: 4. 
     
     
         9 . A pharmaceutical composition comprising the fusion protein of  claim 1 , a protein complex comprising the fusion protein of  claim 1  and an IL-15, a nucleic acid molecule encoding the fusion protein of  claim 1  or a host cell comprising the nucleic acid molecule, or one or more nucleic acid molecules encoding the fusion protein of  claim 1  and an IL-15 or one or more host cells comprising the one or more nucleic acid molecules, and a pharmaceutically acceptable excipient, diluent, or carrier. 
     
     
         10 . A fusion protein comprising the amino acid sequence of SEQ ID NO: 1. 
     
     
         11 . A protein complex comprising the fusion protein of  claim 10  and an IL-15. 
     
     
         12 . The protein complex of  claim 11 , wherein the IL-15 comprises the amino acid sequence of SEQ ID NO: 3. 
     
     
         13 . The protein complex of  claim 11 , wherein the IL-15 comprises the amino acid sequence of SEQ ID NO: 4. 
     
     
         14 . A pharmaceutical composition comprising the fusion protein of  claim 10 , a protein complex comprising the fusion protein of  claim 10  and an IL-15, a nucleic acid molecule encoding the fusion protein of  claim 10  or a host cell comprising the nucleic acid molecule, or one or more nucleic acid molecules encoding the fusion protein of  claim 10  and an IL-15 or one or more host cells comprising the one or more nucleic acid molecules, and a pharmaceutically acceptable excipient, diluent, or carrier. 
     
     
         15 . A fusion protein comprising the amino acid sequence of SEQ ID NO: 2. 
     
     
         16 . A protein complex comprising the fusion protein of  claim 15  and an IL-15. 
     
     
         17 . The protein complex of  claim 16 , wherein the TL-15 comprises the amino acid sequence of SEQ ID NO: 3. 
     
     
         18 . The protein complex of  claim 16 , wherein the IL-15 comprises the amino acid sequence of SEQ ID NO: 4. 
     
     
         19 . A pharmaceutical composition comprising the fusion protein of  claim 15 , a protein complex comprising the fusion protein of  claim 15  and an IL-15, a nucleic acid molecule encoding the fusion protein of  claim 15  or a host cell comprising the nucleic acid molecule, or one or more nucleic acid molecules encoding the fusion protein of  claim 15  and an IL-15 or one or more host cells comprising the one or more nucleic acid molecules, and a pharmaceutically acceptable excipient, diluent, or carrier. 
     
     
         20 . A protein complex comprising an IL-15 having the amino acid sequence of SEQ ID NO: 3, and a fusion protein having an interleukin-15 (IL-15) receptor α sushi domain fused to an Fc monomer, wherein the IL-15 receptor α sushi domain consists of the amino acid sequence of SEQ ID NO: 5, the Fc monomer consists of the amino acid sequence of SEQ ID NO: 6, and the carboxyl-terminus of the IL-15 receptor α sushi domain is fused to the amino-terminus of the Fc monomer via a linker having the amino acid sequence of SEQ ID NO: 7. 
     
     
         21 . The protein complex of  claim 20 , wherein the IL-15 consists of the amino acid sequence of SEQ ID NO: 3. 
     
     
         22 . The protein complex of  claim 20 , wherein the fusion protein consists of the amino acid sequence of SEQ ID NO: 1. 
     
     
         23 . The protein complex of  claim 20 , wherein the fusion protein consists of the amino acid sequence of SEQ ID NO: 2. 
     
     
         24 . A pharmaceutical composition, comprising the protein complex of  claim 20 , one or more nucleic acid molecules encoding the protein complex, or one or more host cells comprising the one or more nucleic acid molecules, and a pharmaceutically acceptable excipient, diluent, or carrier. 
     
     
         25 . A nucleic acid molecule encoding the fusion protein of  claim 1 . 
     
     
         26 . A host cell comprising the nucleic acid molecule of  claim 25 . 
     
     
         27 . A method of producing the fusion protein, comprising culturing the host cell of  claim 26  under conditions sufficient to express the fusion protein, and isolating the fusion protein. 
     
     
         28 . One or more nucleic acid molecules, encoding the fusion protein and the IL-15 of the protein complex of  claim 3 . 
     
     
         29 . One or more host cells comprising the one or more nucleic acid molecules of  claim 28 .